Interview with Help Stop TB team

Learn about the current state and future plans of Help Stop TB through this brief interview

Dear volunteers, Help Stop Tuberculosis team has been collaborating with World Community Grid for nearly six years, and has produced life-saving research results thanks to you. We hope you find this interview-style article informative and answer all of the questions you may have about their research!

What does your project aim to do?

Our project aims to study the structural and organizational properties of Mycolic Acids: very long fatty acids integral to TB's drug resistance. Mycolic Acids are far longer than many other lipids, allowing them to fold into complex structures that a regular fatty acid could not. Mycobacterium tuberculosis bacteria use these complex structures to create a near impenetrable cell wall by fitting Mycolic Acids together like puzzle pieces, preventing drugs and our immune cells from doing their jobs effectively.

We create simulations of Mycolic Acids folding over time to map out their folding behavior and understand how the shapes they adopt change the properties they display - however, to do this we need to generate hundreds of potential combinations of different acids, under different temperature and solvent conditions. This is where the World Community Grid is essential, as such large-scale simulations and analysis would not be possible without the help of many volunteers to provide the computing power.

Our work comes with a range of exciting potential future applications: Firstly, understanding how Mycolic Acids strengthen the cell wall will enable more informed drug design. If we know how it works, we can learn how to break it! Secondly, we can use the knowledge gained on the Mycolic Acids to design our own resilient cell walls (for example in industrially-used microbes to make them more robust), and more broadly to benefit research into other highly flexible and “bendy” molecules.


How was the project affected by the WCG downtime period?

The downtime has allowed us to consolidate the data computed by WCG thus far, and allowed us to further develop the ideas for new aspects of the research, including our own "wiggle parameter" to describe the flexibility of the molecules. We've also had an integral and valued team-member, Christof Jäger, leave the project for new pastures, so we have been carefully planning our next steps to accommodate this loss.


What has your research achieved so far?

Through the volunteers' help, we have one of the largest flexible molecular dynamics data sets and have made rapid progress on understanding highly challenging dynamic systems. This opens up new uses for machine learning and provides different perspectives on the problem of clustering data - a major difficulty at present. It offers us the potential for new perspectives on other exciting chemical systems that have been to date difficult to analyze due to their dynamics, such as intrinsically disordered proteins.


What can the volunteers do?

We appreciate the support and enthusiasm of the volunteers in the forums - the moral support is invaluable when the science gets challenging. Volunteers can always help further when they raise awareness in the community of the valuable WCG projects and their wider impact. This is particularly important for our project as we are seeing a resurgence of TB worldwide on the back of the COVID pandemic. Here, education on how harmful the disease can be, why we are seeing antibiotic resistance, and the importance of global vaccination programmes is key.


Are there any expansions or new projects being considered for the near future?

On the back of the new analytical tools we have been developing with the current dataset, we are considering expanding our molecules to the pathogenetically important cord-factors - medically important derivatives of the mycolic acids we have already looked at. This will provide additional insight into how the chemical coupling of mycolic acids changes their behavior and allows us to further develop our ideas around cell-wall models for TB.

Thank you to Dr. Anna K. Croft  for your contribution, as well as the rest of the HSTB team for their part in building a better world.

The World Community Grid team